Abnormalities in cardiovascular development are responsible for a broad spectrum of heart diseases, yet we known relatively little about the processes that bring about the shape and function of the heart. The proposed research involves the study of the determinants of early cardiac development in zebrafish. Specifically, the study will investigate the transcription factor Myocyte-specific Enhancer-binding Factor 2 (MEF2). The MEF2 protein binds to the MEF2 DNA domain that is found in the enhancers or promoters of most cardiac and skeletal muscle genes. MEF2 is expressed in a tissue-specific manner and may serve as a regulatory protein in cardiac development. MEF2 has recently been cloned from human cardiac and skeletal muscle and shows a high degree of homology to the MADS family of transcriptional activators and homeotic genes. Three MEF2 genes have recently been identified in zebrafish. These MEF2 proteins are highly homologous to the human counterparts. We will determine the spatial and temporal expression of MEF2 in zebrafish embryos and compare the expression pattern to the expression of homeobox genes and structural genes. We will confirm the role of MEF2 in development by disrupting the normal pattern of MEF2 expression. Zebrafish was chosen for this study because its cardiovascular system is easily observed during development and resembles that of the mammalian fetus. Zebrafish embryos are readily manipulated and the genetics are well studied and amenable to disruption.